Studies in this laboratory and others indicated that 72 kd type IV collagenase (MMP-2) plays a role in migration and proliferation of the arterial SMC of animal. To determine whether this enzyme might be involved in human atherosclerosis, human aortic tissue was collected from autopsies of non-cardiovascular death patients. The MMP-2 was visualized in frozen sections of the aortic wall by an immuno-fluorescent staining technique wit antibody prepared against MMP-2. The quantity of this enzyme was also analyzed by the Western blot technique. Results revealed a greater amounts of MMP-2 in fatty streaks and atherosclerotic lesions than found in normal regions of the aorta. Data suggest that 72 kd type IV collagenase may have a role in promoting early atherosclerotic lesion formation, i.e. from fatty streak to plaque. In addition, the increase in expression of the enzyme in the plaque may be involved in complications of atherosclerosis, such as rupture and ulceration. Since bFGF is a major growth factor involved in SMC proliferation after endothelial injury in animal models, cell biological response of human SMC to this growth factor were undertaken. Immunofluorescent staining was used to investigate bFGF nuclear translocation in normal growing and confluent SMC. Also, the expression of Ca2+/calmodulin-dependent protein kinase II (CaM-KII) on the activity of which is necessary for migration in rat SMC and its intracellular distribution in the human SMC were studied following bFGF stimulation. Preliminary results indicate that growing SMC have a quicker response to bFGF, demonstrated as a rapid translocation of bFGF into the nucleus, than do confluent growth arrested cells. Furthermore, bFGF promotes a longer expression of activated nuclear CaM-KII in the growing SMC as compared to confluent SMC. These results provide evidence of specific responses to bFGF stimulation in growing and confluent SMC.